Expression of c-myc mRNA in the Hippocampus of Pentylenetetrazol Kindling Rat

Lee, Jang Chull; Son, Eun Ik; Kim, In Hong; Lee, Sang Do

Abstract

Kindling development is a good animal model of epilepsy and neural plasticity. It is induced by repeated subconvulsive electrical or chemical stimulations. This leads to progressive and permanent amplification of seizure activity resulting in permanent brain changes. Immediate early genes(IEGs) are proposed as the master switch for turning on molecular events in long term neural plasticity. The role of c-myc, an IEG, in the development of kindling is not known. This study was conducted to investigate the role of c-myc in the neural plastic changes underlying kinding. Among 115 adult male Spargue-Dawley rats, 51 were kindled by repeated administrations of subconvulsive doses(15-25mg/kg) of pentylenetetrazol(PTZ). Twenty-eight rats experienced various degree of convulsions induced by a single injection of convulsive dose(30-60mg/kg) of PTZ. Eighteen rats experienced mild or severe convulsions induced by a single injection of convulsive dose(30-60mg/kg) of PTZ. Eighteen rats experienced mild or severe convulsion by a single electroconvulsive shock(ECS). Eighteen rats received normal saline as a control group. Animals were sacrificed in 30 minutes, 1 hour and 48 hours after convulsion. C-myc mRNA levels in the hippocampus were quantified using slot-blot hybridization analysis. In the experiment of PTZ kindling, c-myc mRNA expression 30 minutes after convulsion was elevated about 3-8 times compared with controls. C-myc mRNA expression 1 hour after convulsion was elevated about 4 times at stage I, II, and V, ut was not elevated at stage III and IV. C-myc mRNA expression 48 hours after convulsion was elevated about 2-3 times compared with controls. In the experiment of PTZ-induced seizures, c-myc mRNA expression 30 minutes after convulsion was elevated 5-6 times compared with controls. C-myc mRNA expression 1 hour after convulsion was elevated 4-6 times. C-myc mRNA expression 48 hours after convulsion was elevated approximately 2 times. In the experiment of ECS-induced seizures, c-myc mRNA expression was elevated 4 times at 30 minutes and 1 hour after mild convulsion, but decreased at 30 minutes and 1 hour after severe convulsion compared with control. C-myc mRNA expression 48 hours after convulsion was elevated approximately 2 times. These results suggest that the enhanced expression of c-myc mRNA is a non-specific consequence in the development of PTZ kindling. In addition, c-myc does not seem to play an important role in turning on a molecular program underlying kindling.